Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT04867564 |
| Other study ID # |
20/WIM/2021 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
May 1, 2021 |
| Est. completion date |
May 1, 2024 |
Study information
| Verified date |
July 2021 |
| Source |
Military Institute of Medicine, Poland |
| Contact |
Joanna Socha, MD, PhD |
| Phone |
888302360 |
| Email |
jsocha[@]wim.mil.pl |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Despite the growing interest in investigating how the radiotherapy (RT) dose to anatomical
substructures of the heart links to survival, the heart substructures at risk remain poorly
defined. They are not delineated routinely as part of the RT planning process and there is no
consensus on their dose constrains. With improving prognosis for non-small cell lung cancer
(NSCLC) patients, the evidence relating irradiation of the heart to excess mortality has
begun to accumulate.
The study aims to evaluate subclinical cardiac dysfunction in consecutive NSCLC patients
treated with definitive RT and to investigate the predictive value of the heart substructures
dosimetric parameters for subclinical and overt cardiac toxicity as assessed using
traditional and speckle tracking echocardiography (STE). The study will also investigate
whether subclinical alterations detected by echocardiography with strain imaging may serve as
a marker for future clinical dysfunctions.
Description:
BACKGROUND Radiation-induced cardiac toxicity after RT for breast cancer or haematological
malignancies is well described, with various studies linking post-RT cardiac morbidity and
mortality with radiation dose. In patients treated with RT for NSCLC the associated heart
exposure is higher than in breast cancer patients, and may lead to side effects possibly
reducing survival. With improving prognosis for these patients after RT, the evidence began
to accumulate that overall survival (OS) after RT for NSCLC is related to the heart dose. A
landmark randomized trial Radiation Therapy Oncology Group (RTOG) 0617 failed to show any OS
benefit with higher RT dose, and a post-hoc analysis revealed that the heart dose was a
strong predictor of inferior OS. However, heart doses are higher with lower lobe tumors
irradiation where irradiated volumes are larger due to respiratory tumor motion, and better
blood supply of these parts of the lungs makes the lung toxicity worse, which also affects
survival. Moreover, higher heart doses result from larger target volumes, which are
themselves associated with worse OS. Therefore, a prospective evaluation of the cardiac
toxicity after RT for NSCLC is needed to determine whether there is a correlation between the
RT dose and specific types of cardiotoxicities.
Cardiac toxicity may manifest as any of a broad spectrum of diseases: as congestive heart
failure, coronary ischemia, arrythmias or conduction abnormalities, and valvular and
pericardial disease, therefore it is important to evaluate dosimetric parameters of the
cardiac substructures, and to correlate them with potential adverse effects. Retrospective
data suggests that the predictive value for cardiac events of the doses for the corresponding
heart substructures outperforms the whole heart doses. STE is a valuable tool for a
quantitative analysis of the changes to the cardiac substructures. Global longitudinal strain
(GLS) has been regarded as a more accurate and sensitive parameter than left ventricle
ejection fraction in assessing cardiac dysfunction, and its utility in the identification of
subclinical myocardial changes has been demonstrated in a variety of conditions, including
hypertension, diabetes mellitus, Cushing's disease, and chemotherapy- and RT-related
cardiotoxicity. Recently, GLS has also been proved useful in the evaluation of the function
of both atria and a right ventricle. Thus, STE is a non-invasive method allowing not only for
the identification but also for the quantitative evaluation of subclinical systolic
dysfunction of all the heart chambers.
In the present study, subclinical myocardial dysfunction will be evaluated using STE before
and 1, 6, and 12 months after RT in consecutive NSCLC patients treated with definitive RT
with or without chemotherapy (CHT) and the association between early cardiac effects and RT
dose distribution in the corresponding heart substructures will be explored. Moreover, the
study will show whether subclinical alterations detected by strain imaging precede the
occurrence of clinical dysfunctions, possibly allowing for earlier treatment or closer
monitoring of such patients.
OBJECTIVES OF THE STUDY The aim of this prospective study is to evaluate subclinical cardiac
dysfunction in consecutive NSCLC patients treated with definitive RT and to investigate the
predictive value of the cardiac substructures dosimetric parameters for cardiac toxicity as
evaluated using STE and traditional echocardiographic parameters. The study will also
investigate whether subclinical alterations detected by echocardiography with strain imaging
may serve as a marker for future clinical dysfunctions.
